a phase 3, multi-center study evaluating pl9643 in patients with dry eye

Conditions: Dry Eye; Dry Eye Syndromes

Summary: this is a multi-center, double-masked, randomized, vehicle-controlled study testing pl9643, an ophthalmic solution to determine if safe and efficacious for dry eye patients. after a 2-week run-in period, patients will be randomized equally to the pl9643 ophthalmic solution or vehicle ophthalmic solution administered bilaterally three times a day for 12 weeks. a data monitoring committee was engaged to review interim data.

this is a multi-center, double-masked, randomized, vehicle-controlled study testing pl9643, an ophthalmic solution, to determine the safety and efficacy against a vehicle in dry eye patients. during a 2-week/14-day study run-in period (for the purpose of subject selection) prior to randomization, all subjects will receive vehicle ophthalmic solution (vehicle) bilaterally three times a day. randomization will then occur in a 1:1 ratio where patients will be assigned to receive pl9643 ophthalmic solution given bilaterally three times a day or vehicle ophthalmic solution administered bilaterally three times a day. the treatment period is 12 weeks.

Eligibility criteria:
inclusion criteria: 1. be at least 18 years of age; 2. provide written informed consent; 3. be willing and able to comply with all study procedures; 4. have a patient-reported history of dry eye for at least 5 years prior to visit 1; 5. have a history of use or desire to use eye drops for dry eye symptoms within 6 months of visit 1; 6. have a best corrected visual acuity (bcva) of 0.7 logarithm of the minimum angle of resolution (logmar) or better (snellen equivalent score of 20/100 or better) in each eye at visit 1; 7. have an inferior fluorescein corneal staining score \> 1 at both visits 1 and 2 pre-cae®; 8. have an eye discomfort from the visual analog scale (vas) ≥25 at both visits 1 and 2 pre-cae®; 9. report a score of ≥ 2 according to the ora calibra® ocular discomfort \& 4-symptom questionnaire in at least one of the dry eye symptoms at visits 1 and 2 pre-cae®; 10. have a schirmer's test score of ≤ 10 mm and ≥ 1 mm at visits 1 and 2; 11. have a corneal fluorescein staining score of ≥ 2 in any corneal region (inferior, central or superior) according to the ora calibra® corneal and conjunctival staining scale for grading of fluorescein staining in at least one eye at visits 1 and 2 pre-cae®; 12. have a conjunctival redness score ≥ 1 according to the ora calibra® conjunctival redness for dry eye scale in at least one eye at visits 1 and 2 pre-cae®; 13. demonstrate in the same eye(s) a response to the cae®at visits 1 and 2 as defined by: 1. having at least a ≥1 point increase in fluorescein staining in the inferior region in at least one eye following cae® exposure; 2. reporting an ocular discomfort score ≥3 at 2 or more consecutive time points in at least one eye during cae® exposure (if a subject has an ocular discomfort rating of 3 at time = 0 for an eye, s/he must report an ocular discomfort rating of 4 for two consecutive measurements for that eye). note: a subject cannot have an ocular discomfort score of 4 at time = 0); 14. have at least one eye, the same eye, satisfy all criteria for 7, 8, 9, 10, 11, 12 and 13 above; 15. a negative urine pregnancy test if female of childbearing potential (those who are not surgically sterilized \[bilateral tubal ligation, hysterectomy or bilateral oophorectomy\] or post-menopausal \[12 months after last menses\]) and must use adequate birth control through the study period. for non-sexually active females, abstinence may be regarded as an adequate method of birth control exclusion criteria: 1. have any clinically significant slit-lamp findings at visit 1 that may include active blepharitis, meibomian gland dysfunction, lid margin inflammation, or active ocular allergies that require therapeutic treatment, and/or in the opinion of the investigator may interfere with study parameters; 2. be diagnosed with an ongoing ocular infection (bacterial, viral, or fungal), or active ocular inflammation at visit 1 or visit 2; 3. have worn contact lenses within 7 days of visit 1 or anticipate using contact lenses during the study; 4. have previously had laser-assisted in situ keratomileusis (lasik) surgery within the last 12 months; 5. have used restasis®, xiidra®, cequa®, or eysuvis® within 60 days of visit 1; 6. have had any ocular and/or lid surgeries in the past 6 months or have any planned ocular and/or lid surgeries over the study period; 7. have had any laser procedures (e.g. yag capsulotomy) in the past 3 months; 8. be using or anticipate using temporary punctal plugs during the study that have not been stable within 30 days of visit 1; 9. be currently taking any topical ophthalmic prescription (including medications for glaucoma) or over-the-counter solutions, artificial tears, gels or scrubs, and cannot discontinue these medications for the duration of the trial (excluding medications allowed for the conduct of the study); the respective wash-out periods are required for thefollowing medications: 1. ocular, oral or nasal antihistamines: 72 hours prior to visit 1 and during the study. 2. oral aspirin or aspirin-containing products allowed if dose has been stable over past 30 days prior to visit 1 and no change in dose is anticipated during the study period 3. corticosteroids or mast cell stabilizers (including ocular): 14 days prior to visit 1 4. any medication (oral or topical) known to cause ocular drying that has not been administered as a stable dose for at least 30 days prior to visit 1 and during the study 5. all other topical ophthalmic preparations (including artificial tear substitutes) other than the study drops: 72 hours prior to visit 1 10. have an uncontrolled systemic disease; 11. be a woman who is pregnant, nursing, or planning a pregnancy; 12. be unwilling to submit a urine pregnancy test at visit 1 and visit 6 (or early termination visit) if of childbearing potential. non-childbearing potential is defined as a woman who is permanently sterilized (e.g., bilateral tubal ligation, hysterectomy or bilateral oophorectomy), or is post-menopausal (without menses for 12 consecutive months); 13. be a woman of childbearing potential who is not using an acceptable means of birth control; acceptable methods of contraception include: hormonal - oral, implantable, injectable, or transdermal contraceptives; mechanical - spermicide in conjunction with a barrier such as a diaphragm or condom; intrauterine device; or surgical sterilization of partner. for non-sexually active females, abstinence may be regarded as an adequate method of birth control; however, if the subject becomes sexually active during the study, she must agree to use adequate birth control as defined above for the remainder of the study; 14. have a known allergy and/or sensitivity to the test article or its components; 15. have a condition or be in a situation which the investigator feels may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject's participation in the study; 16. have used an investigational drug or device within 30 days of visit 1 unless the investigator or sponsor deems a washout period of up to 60 days is required; 17. participated in a previous clinical study involving pl9643; 18. be unable or unwilling to follow instructions, including participation in all study assessments and visits.

Keywords: dry eye ophthalmology eye diseases corneal diseases conjunctival diseases ophthalmic solutions pharmaceutical solutions